The nonmuscle
myosin II motor
protein produces forces that are essential to driving the cell movements and cell shape changes that generate tissue structure. Mutations in
myosin II that are associated with human diseases are predicted to disrupt critical aspects of
myosin function, but the mechanisms that translate altered
myosin activity into specific changes in tissue organization and physiology are not well understood. Here we use the Drosophila embryo to model human disease mutations that affect
myosin motor activity. Using in vivo imaging and biophysical analysis, we show that engineering human
MYH9-related disease mutations into Drosophila
myosin II produces motors with altered organization and dynamics that fail to drive rapid cell movements, resulting in defects in epithelial morphogenesis. In embryos that express the Drosophila
myosin motor variants R707C or N98K and have reduced levels of wild-type
myosin,
myosin motors are correctly planar polarized and generate anisotropic contractile tension in the tissue. However, expression of these motor variants is associated with a cellular-scale reduction in the speed of cell intercalation, resulting in a failure to promote full elongation of the body axis. In addition, these
myosin motor variants display slowed turnover and aberrant aggregation at the cell cortex, indicating that mutations in the motor domain influence mesoscale properties of
myosin organization and dynamics. These results demonstrate that disease-associated mutations in the
myosin II motor domain disrupt specific aspects of
myosin localization and activity during cell intercalation, linking molecular changes in
myosin activity to defects in tissue morphogenesis.